Microparticles

Abstract

A method of forming particles comprises accelerating a stream comprising a liquid; and vibrating the stream, to form particles. The particle may have a diameter that is smaller than the diameter of the nozzle used to form the stream, allowing for the formation of micro- and nano-sized particle.

Description

[0001] The present application claims the benefit of two provisional applications, Provisional application serial No. 60 / 225,525 filed Aug. 15, 2000, to Kyekyoon Kim and Daniel W. Pack, entitled "PRECISE, CONTROLLED POLYMER FABRICATION FOR BIOMEDICAL APPLICATIONS"; and Provisional application serial No. 60 / 225,620 filed Aug. 15, 2000, to Kyekyoon Kim, entitled "APPARATUS AND METHOD FOR FABRICATION OF UNIFORM SOLID AND HOLLOW SPHERICAL PARTICLES IN THE MICRON- AND SUBMICRON-RANGE AND SUCH PARTICLES OF CONTROLLED SIZES, ELECTRICAL CHARGES, CHEMICAL COMPOSITIONS AND STOICHIOMETRIES USING FIELD-INJECTION CHARGING AND ELECTROHYDRODYNAMIC SPRAYING"; both of which are hereby incorporated by reference.[0002] Rapid advances in biotechnology have led to the discovery of numerous protein and peptide therapeutics, many of which have recently reached the marketplace or are currently under regulatory review by the United States Food and Drug Administration. Unlike traditional small-molecule drugs...

AI Technical Summary

Benefits of technology

[0020] It is yet a further object of this invention to provide a novel process for hardening micro-and nano-spheres by utilizing any of the above processes for producing micro-and nano-spheres, wherein the nozzle or orifice utilized is placed beneath the surface of an aqueous bath, to allow hardening of the spheres with a minimum of deformation.

[0107] Control of drug release rate from microshells. Encapsulation of water-soluble compounds in hydrophobic polymer microspheres typically requires a double-emulsion method in which a drug / aqueous phase is emulsified with a polymer / oil phase. The physical forces necessary for forming the water-in-oil emulsion and contact of the drug with the aqueous / oil interface can be damaging to drug compounds including therapeutic proteins and nucleic acids. Encapsulation in microshells can alleviate this problem as no physical forces are employed and the aqueous / oil interface is greatly reduced in area.

Problems solved by technology

Unlike traditional small-molecule drugs, however, proteins and peptides generally cannot be administered orally; injection or infusion is most often required.

Sphere size and size distribution are reproducible but often poorly controllable.

Spheres that are "too small" exhibit poor encapsulation efficiency, may migrate from the site of injection, and may exhibit undesirably rapid release of their payload.

Spheres that are "too large" may not easily pass through a syringe needle.

Thus, the typically polydisperse spheres generated by conventional fabrication techniques must be filtered or sieved to isolate particles within the desired size range, and the polymer and drug composing spheres outside that range are wasted.

The success of the latter studies was limited by the relatively broad microsphere size distributions.

However, none of these methods was successful in generating particles in a size range appropriate for drug delivery (.about.1-100 .mu.m) while maintaining narrow size distributions.

In addition, these previous methods appear to be difficult to scale-up for commercial applications.

This in turn indicates practical difficulties associated with fabricating uniform solid and hollow spheres of small sizes (less than about 50 .mu.m in diameter) especially spheres in the submicron-size range.

This problem becomes worse when the materials being used are viscous.

With previous technologies for spraying microdroplets from nozzle-type devices, the minimum sphere size typically obtainable is limited by the size of the nozzle opening.

Usually, it is not possible to make drops smaller than the nozzle opening; typically, droplet diameters are 1-4 times the diameter of the nozzle.

This presents several difficulties as the desired sphere size decreases.

One problem is that fabrication of the nozzles themselves becomes more difficult as size decreases.

A second limitation stems from the pressure needed to pump fluids through small nozzles.

This is clearly an impossibly high pressure.

Another problem with traditional methods of forming small spheres is that some compounds to be encapsulated, such as plasmid DNA, may be damaged by shear forces.

However, entrance effects will tend to increase the shear rate meaning this equation will give a low estimate.

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